Amniotic fluid (AF) is a complex and dynamic milieu that changes as pregnancy progresses. AF contains nutrients and growth factors that facilitate fetal growth, provides mechanical cushioning and antimicrobial effectors that protect the fetus, and allows assessment of fetal maturity and disease.
AF contains a plethora of factors including carbohydrates, proteins and peptides, lipids, lactate, pyruvate, electrolytes, enzymes, and hormones. AF contains many important growth factors including epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), transforming growth factor beta-1, insulin-like growth factor I (IGF-I), and erythropoietin (EPO).
Human AF contains factors that appear to minimize scarring (Ozgenel G Y et al., J Neurosurg 2003; 98: 371-377). Amniotic factors that potentially contribute to the wound healing process include hyaluronic acid, which is found in high levels in AF, inhibits collagen synthesis. This hyaluronic acid-rich environment is due to a relative lack of hyaluronidase in AF and to the presence of hyaluronic acid-stimulating factor in AF. In one study looking at the effect of AF on proteases important to wound healing, human AF was shown to enhance collagenase activity, but to inhibit activities of hyaluronidase, elastase, and cathepsin (Gao X et al., Ann Plastic Surg 1994; 33: 128-134). In addition, TGF-β may also play a major role in scar formation (Adzick NsS et al., Ann Surg 1994; 220: 10-18).
Furthermore, human AF has been evaluated as a source for stem cells (In't Anker P S et al., Blood 2003; 102: 1548-1549).
It is unclear whether important amniotic factors can survive processes such as centrifugation, filtration, refrigeration, freezing, and long-term storage.
Therefore, it is an objective of the current invention to provide methods for enhancing the stability of amniotic fluids for long-term storage at temperatures above freezing.
It is also an objective of the current invention to provide methods for purification of amniotic fluid that maximize the stability of critical amniotic factors present in the raw amniotic fluid for therapeutic applications.
It is a further objective of this current invention to provide dosage units and formulations that are readily accessible and easy to use for both the clinician and patient, as well as new uses thereof.